Recognition of single-stranded RNA viruses by Toll-like receptor 7

Recognition of single-stranded RNA viruses by Toll-like receptor 7
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DOI:
10.1073/pnas.0400937101
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发表时间:
2004-04-13
影响因子:
11.1
通讯作者:
Flavell, RA
Flavell, RA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lund, JM;Alexopoulou, L;Flavell, RA

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哺乳动物宿主的病毒感染导致先天免疫反应的激活。 Toll 样受体 (TLR) 已被证明可以介导多种类型病原体的识别,包括病毒。病毒基因组具有哺乳动物基因组中所没有的独特特征,例如高CpG含量和双链RNA。这些基因组核酸充当与病毒感染相关的分子特征。在这里,我们证明TLR7识别单链RNA病毒、水泡性口炎病毒和流感病毒。浆细胞样树突状细胞和 B 细胞通过 TLR7 识别这些病毒,导致它们激活共刺激分子并产生细胞因子。此外,这种识别需要完整的内吞途径。缺乏 TLR7 或 TLR 衔接蛋白 MyD88 的小鼠表现出对水泡性口炎病毒体内感染的反应减弱。这些结果证明了 TLR7 的微生物配体识别能力,并提供了对先天免疫细胞识别病毒病原体的途径的深入了解。
Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.